通过……提高肺腺癌对免疫治疗药物的敏感性。（原文不完整，此为根据现有内容翻译）

Enhancing the sensitivity of lung adenocarcinoma to immune therapeutic agents through .

作者信息

Wu Chen, Ma Lingling, Wang Yi, Bidzińska Joanna, Wang Yilang

机构信息

Department of Science and Education, Affiliated Maternity and Child Health Care Hospital of Nantong University, Nantong, China.

2nd Department of Radiology, Medical University of Gdansk, Gdansk, Poland.

出版信息

Transl Lung Cancer Res. 2025 Aug 31;14(8):3076-3089. doi: 10.21037/tlcr-2025-800. Epub 2025 Aug 26.

DOI:10.21037/tlcr-2025-800

PMID:40948827

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12432670/

Abstract

BACKGROUND

Programmed death-ligand 1 (PD-L1), a classic immune checkpoint, is a key target for immunotherapy. Research has demonstrated that Sprouty-related domain-containing 1 (), a negative regulator of the mitogen-activated protein kinase (MAPK) pathway, modulates PD-L1 expression and exhibits antitumor activity in diverse cancers. This study aimed to investigate the role and mechanisms of in enhancing the sensitivity of lung adenocarcinoma (LUAD) to immunotherapy and develop novel clinical therapeutic sensitization strategies.

METHODS

In this study, bioinformatics technologies were employed to examine the interaction between and the survival prognosis of patients with LUAD and to identify key interacting molecules of . The expression levels of in LUAD tissues were measured by tissue staining, Western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier analysis was used to confirm the correlation between and the prognosis of patients with LUAD. Moreover, Cell Counting Kit-8 (CCK-8), colony formation, wound healing, and Transwell assays were conducted to investigate the effects of on LUAD cell function and immunotherapy.

RESULTS

Bioinformatics analyses revealed that had a low expression in patients with LUAD and was associated with poor prognosis (P<0.05), suggesting its prominent role in LUAD. Tissue staining, Western blotting, and qRT-PCR demonstrated that was downregulated in LUAD tissues, and its low expression was significantly correlated with poor N stage and advanced pathological stage (P<0.05). Transwell, wound healing, and colony formation assays indicated that suppressed LUAD cell migration and proliferation. Furthermore, the CCK-8 assay confirmed that increases immunotherapeutic sensitivity.

CONCLUSIONS

is downregulated in patients with LUAD and is an independent prognostic factor. enhances PD-L1 expression, thereby mediating its role in enhancing immunotherapeutic sensitivity in LUAD.

摘要

背景

程序性死亡配体1（PD-L1）是一种经典的免疫检查点，是免疫治疗的关键靶点。研究表明，含Sprouty相关结构域蛋白1（SPRY1）作为丝裂原活化蛋白激酶（MAPK）通路的负调控因子，可调节PD-L1表达，并在多种癌症中表现出抗肿瘤活性。本研究旨在探讨SPRY1在增强肺腺癌（LUAD）对免疫治疗敏感性中的作用及机制，并制定新的临床治疗增敏策略。

方法

在本研究中，采用生物信息学技术检测SPRY1与LUAD患者生存预后的相关性，并鉴定SPRY1的关键相互作用分子。通过组织染色、蛋白质印迹法和定量实时聚合酶链反应（qRT-PCR）检测LUAD组织中SPRY1的表达水平。采用Kaplan-Meier分析确定SPRY1与LUAD患者预后的相关性。此外，进行细胞计数试剂盒-8（CCK-8）、集落形成、伤口愈合和Transwell实验，以研究SPRY1对LUAD细胞功能和免疫治疗的影响。

结果

生物信息学分析显示，SPRY1在LUAD患者中表达较低，且与预后不良相关（P<0.05），提示其在LUAD中起重要作用。组织染色、蛋白质印迹法和qRT-PCR表明，LUAD组织中SPRY1表达下调，其低表达与N分期差和病理分期晚期显著相关（P<0.05）。Transwell、伤口愈合和集落形成实验表明，SPRY1抑制LUAD细胞迁移和增殖。此外，CCK-8实验证实SPRY1可提高免疫治疗敏感性。